Biochemical analysis apparatus with an integral centrifuge

ABSTRACT

A biochemical analysis apparatus includes a sample accommodating region, an accommodating region for test films containing a reagent which reacts with a liquid sample to give rise to a change in optical density, and a conveyor for sequentially pulling out each test film from the test film accommodating region. An applicator takes up the liquid sample fromt he sample accommodating region and applies it to the test film at the position to which the test film has been pulled out. An incubator incubates the sample-applied film portion for a predetermined time, and a detector measures the optical density of the sample applied applied film portion during or after the passage of the predetermined time. The conveyor, the incubator and the detector are provided to correspond to each of the test films, and a movement device moves the applicator to apply the liquid sample to the test films.

This is a continuation of application No. 07/420,407 filed Oct. 12, 1989now abandoned, which was a division of application Ser. No. 07/218,398,now abandoned, filed Jul. 13, 1988.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to a biochemical analysis apparatus for applyinga liquid sample to a test film provided with a single reagent layer or aplurality of reagent layers, maintaining the test film at apredetermined temperature (i.e. carrying out incubation) for apredetermined time, and measuring the degree of reaction of the reagentwith the liquid sample during or after the incubation.

2. Description of the Prior Art

Qualitative or quantitative analysis of a specific chemical constituentin a liquid sample is generally conducted for various industrialpurposes. Particularly, it is very important in biochemical and clinicalfields to quantitatively analyze chemical constituents or physicalconstituents in body fluid such as blood or urine.

In recent years, as disclosed in, for example, Japanese PatentPublication No. 53(1978)-21677 and Japanese Unexamined PatentPublication No. 55(1980)-164356, there has been developed and put intopractice a dry type chemical analysis slide for quantitatively analyzinga specific chemical constituent or a specific physical constituentcontained in a liquid sample simply by applying a droplet of the liquidsample. With the chemical analysis slide, it is possible to analyze aliquid sample more simply and more quickly than with the conventionalwet type analysis method. Therefore, the use of the chemical analysisslide is desirable particularly in medical organizations, researchlaboratories, or the like where many samples are to be analyzed.

In order to analyze a chemical constituent or the like contained in aliquid sample by use of the chemical analysis slide, a measured amountof the liquid sample is put on the chemical analysis slide and ismaintained at a predetermined temperature (i.e. incubated) for apredetermined time in an incubator to cause a color reaction. Thechemical analysis slide is then exposed to measuring light having awavelength selected in advance in accordance with the combination of theconstituent of the liquid sample with a reagent contained in the reagentlayer of the chemical analysis slide, and the light reflected by thechemical analysis slide is measured in terms of the optical density. Inthis manner, it is possible to achieve quantitative analysis of thechemical constituent or the like.

In the medical organizations, research laboratories or the like in whichmany liquid samples are to be analyzed, it is desirable that theanalysis be conducted automatically and sequentially. To satisfy thisneed, there have been proposed various chemical analysis apparatuses forcarrying out sample analysis automatically and sequentially by use ofthe aforesaid chemical analysis slides. One of such chemical analysisapparatuses is disclosed in, for example, Japanese Unexamined PatentPublication No. 56(1981)-77746. Also as a means for analyzing liquidsamples automatically and sequentially, there has been proposed in, forexample, U.S. Pat. No. 3,526,480 an apparatus wherein a long tape-liketest film containing a reagent is accommodated instead of the aforesaidchemical analysis slides, and sample application, incubation andmeasurement are carried out sequentially by pulling out the test film.

With the technique wherein a single chemical analysis slide is used fora single measurement, many chemical analysis slides must be processedfor automatically and sequentially carrying out the analysis of liquidsamples, and therefore the apparatus becomes complicated, large andexpensive. On the other hand, the technique wherein the long tape-liketest film containing a reagent is used instead of the chemical analysisslide is advantageous for carrying out measurement automatically andsequentially. However, with the aforesaid conventional apparatus whereina plurality of the long test films are stacked one upon another andconveyed along nearly the same path, the respective long test films areprovided with openings for the purposes of, for example, allowing sampleapplication to a long test film located at a lower part of the stack andpreventing the long test films other than the long test film which isbeing subjected to measurement from obstructing the measurement. As thelong test films must be processed for the provision of the openings, thecost increases, the number of measurement operations possible with asingle long test film decreases, and the running cost of the apparatusincreases. Also, in order to prevent interference of the respective longtest films with one another at the time of the sample application, themeasurement and other steps, conveyance of the long test films must becontrolled in a complicated manner for conveying the long test films ingood sequence.

SUMMARY OF THE INVENTION

The primary object of the present invention is to provide a biochemicalanalysis apparatus which is made simple, small and cheap by employingthe system utilizing a long tape-like test film advantageous forcarrying out measurement automatically and sequentially, which reducesthe running cost by elimination of processing for the provision of anopening in the long test film, and which simultaneously carries outmeasurement of a plurality of measurement items.

Another object of the present invention is to provide a biochemicalanalysis apparatus, which automatically and sequentially carries outoperations from a step of accommodating body fluid prior to thepreparation of a liquid sample and preparing the liquid sample from thebody fluid to a step of analysis of the prepared liquid sample, therebyto increase the operating efficiency and minimizing the possibility of asample processing error arising when a plural kinds of body fluids(liquid samples) are processed simultaneously.

A further object of the present invention is to provide a biochemicalanalysis apparatus which carries out measurement of a plurality ofmeasurement items simultaneously and quickly.

A still further object of the present invention is to provide abiochemical analysis apparatus which has a simple mechanism, thereby tominimize operation failures and reduce the cost, and which has aconfiguration suitable for quick processing.

The present invention provides a first biochemical analysis apparatuscomprising:

i) a sample accommodating means for accommodating a liquid sample,

ii) a test film accommodating means for accommodating a long test filmcontaining a reagent which reacts with said liquid sample to give riseto a change in optical density,

iii) a test film conveyance means for sequentially pulling out said longtest film accommodated in said test film accommodating means,

iv) a sample application means for taking up said liquid sampleaccommodated in said sample accommodating means and applying apredetermined amount of said liquid sample onto said long test film atthe position to which said long test film has been pulled out of saidtest film accommodating means,

v) an incubator for maintaining the sample-applied portion of said longtest film at a predetermined temperature for a predetermined time, and

vi) a detection means for irradiating light to said sample-appliedportion of said long test film and measuring the optical density givenrise to by said reaction during or after the passage of saidpredetermined time,

wherein said test film accommodating means is constituted to accommodatea plurality of the long test films, said test film conveyance means,said incubator and said detection means are provided to correspond toeach of a plurality of said long test films, and a movement means isprovided for moving said sample application means so as to carry out thesample application to the predetermined position on each of a pluralityof said long test films.

The present invention also provides a second biochemical analysisapparatus comprising:

i) a sample accommodating means for accommodating a liquid sample,

ii) a centrifugation means for accommodating body fluid and preparing aliquid sample by centrifugation of the body fluid,

iii) a sample transfer means for transferring said liquid sampleprepared by said centrifugation means to said sample accommodatingmeans,

iv) a test film accommodating means for accommodating a test filmreacting with said liquid sample to give rise to a change,

v) a test film conveyance means for sequentially conveying said testfilm accommodated in said test film accommodating means to apredetermined position outside of said test film accommodating means,

vi) a sample application means for taking up said liquid sample out ofsaid sample accommodating means and applying a predetermined amount ofsaid liquid sample onto said test film conveyed to said predeterminedposition,

vii) an incubator for maintaining the sample-applied portion of saidtest film at a predetermined temperature for a predetermined time, and

viii) a detection means for measuring a change at said sample-appliedportion of said test film during or after the passage of saidpredetermined time.

The present invention further provides a third biochemical analysisapparatus comprising:

i) a sample accommodating means for accommodating a liquid sample,

ii) a centrifugation means for accommodating body fluid and preparing aliquid sample by centrifugation of the accommodated body fluid,

iii) a test film accommodating means for accommodating a test filmreacting with said liquid sample to give rise to a change,

iv) a test film conveyance means for sequentially conveying said testfilm accommodated in said test film accommodating means to apredetermined position outside of said test film accommodating means,

v) a sample application means for taking up said liquid sample out ofone of said sample accommodating means and said centrifugation meansselectively and applying a predetermined amount of said liquid sampleonto said test film conveyed to said predetermined position,

vi) an incubator for maintaining the sample-applied portion of said testfilm at a predetermined temperature for a predetermined time, and

vii) a detection means for measuring a change at said sample-appliedportion of said test film during or after the passage of saidpredetermined time.

The present invention still further provides a fourth biochemicalanalysis apparatus comprising:

i) a sample accommodating means for accommodating a liquid sample andprovided with a centrifuging function for accommodating body fluid andpreparing a liquid sample by centrifugation of the accommodated bodyfluid,

ii) a test film accommodating means for accommodating a test filmreacting with said liquid sample to give rise to a change,

iii) a test film conveyance means for sequentially conveying said testfilm accommodated in said test film accommodating means to apredetermined position outside of said test film accommodating means,

iv) a sample application means for taking up said liquid sample out ofsaid sample accommodating means and applying a predetermined amount ofsaid liquid sample onto said test film conveyed to said predeterminedposition,

v) an incubator for maintaining the sample-applied portion of said testfilm at a predetermined temperature for a predetermined time, and

vi) a detection means for measuring a change at said sample-appliedportion of said test film during or after the passage of saidpredetermined time.

The present invention also provides a fifth biochemical analysisapparatus comprising:

i) a sample accommodating means for accommodating a liquid sample,

ii) a test film accommodating means for accommodating a test filmreacting with said liquid sample to give rise to a change,

iii) a test film conveyance means for sequentially conveying said testfilm accommodated in said test film accommodating means to apredetermined position outside of said test film accommodating means,

iv) a sample application means for taking up said liquid sampleaccommodated in said sample accommodating means and applying apredetermined amount of said liquid sample onto said test film conveyedto said predetermined position,

v) an incubator for maintaining the sample-applied portion of said testfilm at a predetermined temperature for a predetermined time, and

vi) a detection means for measuring a change at said sample-appliedportion of said test film,

wherein said test film accommodating means is constituted to accommodatea plurality of the test films different in their measurement items fromone another in parallel, and said sample application means isconstituted to be capable of accommodating said liquid sample in anamount necessary for the sample application to all of the test films,that correspond to a necessary measurement item among a plurality of themeasurement items, at one time, and to apply said liquid samplesequentially onto said test films corresponding to said necessarymeasurement item.

The present invention further provides a sixth biochemical analysisapparatus comprising:

i) a sample accommodating means for accommodating a liquid sample,

ii) a test film accommodating means for accommodating a test filmreacting with said liquid sample to give rise to a change,

iii) a test film conveyance means for sequentially conveying said testfilm accommodated in said test film accommodating means to apredetermined position outside of said test film accommodating means,

iv) a sample application means for taking up said liquid sample out ofsaid sample accommodating means and applying a predetermined amount ofsaid liquid sample onto said test film conveyed to said predeterminedposition,

v) an incubator for maintaining the sample-applied portion of said testfilm at a predetermined temperature for a predetermined time, and

vi) a detection means for measuring a change at said sample-appliedportion of said test film during or after the passage of saidpredetermined time,

wherein said test film accommodating means is constituted to accommodatea plurality of the test films, said sample application means is providedwith a sample applying nozzle moveable along a straight line or acircular arc, and the liquid sample take-out position at which saidliquid sample is taken up by said sample application means and all ofthe sample applying positions at which said liquid sample is appliedonto a plurality of said test films are disposed on the straight line orthe circular arc corresponding to the movement path of said sampleapplying nozzle.

The term "test film" used herein for the second to sixth biochemicalanalysis apparatuses in accordance with the present invention embracesan electrolyte determination slide (which is used for quantitativelyanalyzing the ionic activity in a liquid sample by applying the liquidsample and a reference solution to the slide, incubating the slide, andthen measuring a difference in potential corresponding to the differencein ionic activity between the liquid sample and the reference solution),a chemical analysis slide, and a long tape-like test film employedinstead of the chemical analysis slide.

With the first biochemical analysis apparatus in accordance with thepresent invention wherein the test film accommodating means isconstituted to accommodate a plurality of the long test films, and thetest film conveyance means, the incubator and the detection means areprovided to correspond to each of a plurality of said long test films,the long test films need not be processed for the provision of openings,and the running cost can be reduced. Also, as the movement means isprovided for moving the sample application means so as to carry out thesample application to the predetermined position on each of a pluralityof the long test films, measurement of a plurality of measurement itemscan be carried out simultaneously by accommodating the long test filmsfor a plurality of the measurement items in the test film accommodatingmeans.

Also, with the first biochemical analysis apparatus in accordance withthe present invention, the test film accommodating means foraccommodating the long test films each containing a reagent which reactswith the liquid sample to give rise to a change in optical density, andcontrolling the unused portions of the long test films at apredetermined temperature and humidity is provided. Each long test filmaccommodated in the test film accommodating means is sequentially pulledout by the test film conveyance means, and the liquid sampleaccommodated in the sample accommodating means is taken up by the sampleapplication means and applied onto the long test film at the position towhich the long test film has been pulled out of the test filmaccommodating means. Thereafter, the sample-applied portion of the longtest film is incubated, the optical density of the incubated portion ofthe long test film is measured by the detection means. Therefore, achange in the optical density produced by the color reaction can bemeasured automatically and sequentially, and the biochemical analysisapparatus can be made simple, small and cheap. Also, in the case wherethe long test film is not used over its overall length in a series ofmeasurements and a film portion remains unused, the remaining unusedportion of the test film can be stored in the biochemical analysisapparatus such that the remaining unused portion does not deteriorateand is usable for the next measurement.

With the second biochemical analysis apparatus in accordance with thepresent invention wherein the centrifugation means is provided, theliquid sample can be prepared from body fluid The liquid sample thusprepared is automatically transferred by the sample transfer means tothe sample accommodating means, taken out of the sample accommodatingmeans, applied onto the test film, incubated and then subjected to themeasurement. Therefore, the operations from the step of preparing theliquid sample from the body fluid to the step of analysis of theprepared liquid sample can be carried out automatically andsequentially, the operating efficiency can be increased, and a sampleprocessing error arising when plural kinds of body fluids (liquidsamples) are processed simultaneously can be minimized.

With the third biochemical analysis apparatus in accordance with thepresent invention, instead of providing the sample transfer means in thesecond biochemical analysis apparatus in accordance with the presentinvention, the sample application means is constituted to take out theliquid sample from one of the sample accommodating means and thecentrifugation means selectively. Therefore, as in the case of thesecond biochemical analysis apparatus in accordance with the presentinvention, the operations from the step of preparing the liquid samplefrom the body fluid to the step of analysis of the prepared liquidsample can be carried out automatically and sequentially, the operatingefficiency can be increased, and a sample processing error arising whenplural kinds of body fluids (liquid samples) are processedsimultaneously can be minimized.

With the fourth biochemical analysis apparatus in accordance with thepresent invention wherein, instead of providing the centrifugation meansindependently of the sample accommodating means as in the second andthird biochemical analysis apparatuses, the sample accommodating meansprovided with the centrifuging function is employed. Therefore, as inthe case of the second and third biochemical analysis apparatuses inaccordance with the present invention, the operations from the step ofpreparing the liquid sample from the body fluid to the step of analysisof the prepared liquid sample can be carried out automatically andsequentially, the operating efficiency can be increased, and a sampleprocessing error arising when plural kinds of body fluids (liquidsamples) are processed simultaneously can be minimized.

With the fifth biochemical analysis apparatus in accordance with thepresent invention, the test film accommodating means is constituted toaccommodate a plurality of the test films different in their measurementitems from one another in parallel, and the sample application means isconstituted to be capable of accommodating the liquid sample in anamount necessary for the sample application to all of the test films,that correspond to a necessary measurement item among a plurality of themeasurement items, at one time, and to apply the liquid samplesequentially onto the test films corresponding to the necessarymeasurement item. Therefore, the operation of accommodating the liquidsample in the sample application means need not be repeated for eachmeasurement item. Also, as the test films are accommodated in parallel,control for conveying the test films is simplified. Accordingly,measurement of a plurality of the measurement items can be carried outsimultaneously and quickly.

With the sixth biochemical analysis apparatus in accordance with thepresent invention, the test film accommodating means is constituted toaccommodate a plurality of the test films, the sample application meansis provided with the sample applying nozzle moveable along a straightline or a circular arc, and the liquid sample take-out position at whichthe liquid sample is taken up by the sample application means and all ofthe sample applying positions at which the liquid sample is applied ontoa plurality of the test films are disposed on the straight line or thecircular arc corresponding to the movement path of the sample applyingnozzle. Therefore, the operations of the sample application means aresimple, the mechanism of a movement means for moving the sampleapplication means can be simplified, operation failures can beminimized, and the cost of the apparatus can be reduced. Also, the timerequired for the movement of the sample application means can beshortened, and processing can be carried out quickly.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view showing an embodiment of the biochemicalanalysis apparatus in accordance with the present invention,

FIG. 2 is a plan view showing the major part of the embodiment shown inFIG. 1,

FIG. 3 is a sectional view taken along line 3--3 of FIG. 2,

FIG. 4 is a graph showing the rates of deterioration of an unused longtest film with the passage of time when the unused long test film ismaintained under various temperature-humidity conditions, in terms ofthe number of days for which the long test film can be stored under suchconditions without becoming unusable for measurement,

FIG. 5 is a sectional view taken along line 5--5 of FIG. 3,

FIG. 6 is a sectional view taken along line 6--6 of FIG. 2,

FIG. 7 is a sectional view taken along line 7--7, of FIG. 2,

FIG. 8 is a flow diagram showing the pipes communicating with a pipe ofa sample application nozzle,

FIG. 9 is a plan view showing another embodiment of the biochemicalanalysis apparatus in accordance with the present invention,

FIG. 10 is a sectional view showing the sample accommodating meansprovided with a centrifuging function, and

FIG. 11 is a plan view showing a further embodiment of the biochemicalanalysis apparatus in accordance with the present invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention will hereinbelow be described in further detailwith reference to the accompanying drawings.

With reference to FIG. 1, a biochemical analysis apparatus 1 is providedwith a transparent cover 2, and a liquid sample, a long tape-like testfilm 3 and the like are fed into and out of the apparatus 1 by openingthe cover 2. The apparatus 1 is provided with a sample accommodatingmeans 4 for accommodating a liquid sample such as blood serum or urinealong a ring-like area, and the liquid sample is taken up from thesample accommodating means 4 and applied by a sample application means 5as will be described later. A centrifugation means 6 is provided inwardfrom the sample accommodating means 4 for accommodating body fluid, forexample, blood (whole blood), and centrifuging the blood to produceblood serum as the liquid sample, and for other purposes. The long testfilm 3 contains a reagent undergoing a color reaction with only aspecific chemical constituent or a specific physical constituent that isto be analyzed in the liquid sample, and many kinds of the long testfilms are prepared in accordance with the measurement items. An unusedportion of the long test film 3 which has not yet been used formeasurement is wound up in a film feed cassette 7, and the used portionof the long test film 3 which has already been used for measurement iswound up in a film wind-up cassette 8. The lot number, film number,measurement item, working life and other information on the long testfilm 3 are indicated by, for example, a bar code 9, on one face of thefilm wind-up cassette 8. At the center of a reel 10 in the film wind-upcassette 8, a hole 11 is provided for engagement with a rotation shaftof a motor for pulling the long test film 3 out of the film feedcassette 7 after the long test film 3 has been accommodated in thebiochemical analysis apparatus 1 as will be described later. The longtest film 3 is accommodated in the biochemical analysis apparatus 1 inthe form wound up in the film feed cassette 7 and the film wind-upcassette 8. As shown in FIG. 1, the film feed cassette 7 and the filmwind-up cassette 8 are formed independently of each other. A test filmaccommodating means 12 accommodates unused portions of a plurality ofthe long test films 3 in parallel so that various items of measurementscan be carried out simultaneously by use of the apparatus 1. At theright end of the test film accommodating means 12 in FIG. 1, anelectrolyte determination slide accommodating region 14 is provided foraccommodating electrolyte determination slides for determination ofelectrolytes such as Na⁺, K⁺ and Cl⁻ in the liquid sample. The unusedslides are stacked in the accommodating region 14. The sampleapplication means 5 is provided with a sample applying nozzle 15 at theend, and is moved in the extending direction of a rail 16 by a movementmeans 17 placed on the rail 16 for taking up the liquid sample from thesample accommodating means 4 or the centrifugation means 6, and applyingthe liquid sample onto the long test film 3 pulled out by a test filmconveyance means from the test film accommodating means 12 or onto theelectrolyte determination slide pushed out of the electrolytedetermination slide accommodating region 14. The movement means 17 alsomoves the sample application means 5 vertically. The sample applicationmeans 5 is kept at its upper position at the time it is moved by themovement means 17 in the extending direction of the rail 16, and ismoved down at the time of taking out and application of the liquidsample and at the time of washing as will be described later.

In this specification, both the electrolyte determination slide and thelong test film 3 are generically referred to as the test film.

After applying the liquid sample onto the test film, the sample applyingnozzle 15 is washed at a nozzle washing region 18 provided close to theelectrolyte determination slide accommodating region 14 and the sampleaccommodating means 4 therebetween in accordance with the operationsequence as will be described later, and is reused for sampleapplication.

The test film on which the liquid sample has already been applied isincubated by an incubator as will be described later, and subjected tomeasurement by a measurement means.

Control of operations of the overall apparatus 1, processing of themeasurement data and the like are carried out by a circuit region 19 anda computer 20 connected therewith. An operating and display region 21 onthe front surface of the circuit region 19 is provided with a powersource switch for the apparatus 1, an ammeter for monitoring the currentconsumption in the apparatus 1, and other members. The computer 20 isprovided with a keyboard 22 for giving instructions to the apparatus 1,a CRT display device 23 for displaying the subsidiary information forinstructions, measurement results and other items, a printer 24 forprinting the measurement results, and a floppy disk drive unit 25 foraccommodating a floppy disk for storage of commands for giving variousinstructions to the apparatus 1 and the information on the measurementresults.

With reference to FIG. 2 showing the major part of the apparatus 1, thetest film accommodating means 12 is constituted so that sample applyingpositions 41 41' and 41" for all of the test films pulled out or pushedout of the test film accommodating means 12 stand in a straight lineindicated by the chain line. Also, the nozzle washing region 18, aliquid sample take-out position 40a in the sample accommodating means 4,and a liquid sample take-out position 42a in the centrifugation means 6are disposed on said straight line. The arrangement on the straight linesimplifies the configuration of the movement means as will be describedlater, which in turn contributes to a decrease in operation failures andcost of the apparatus 1.

The sample accommodating means 4 accommodates a plurality of liquidsamples in accommodating regions 40 disposed in the ring-like area. Theaccommodating regions 40 are automatically rotated along the circularpath until the liquid sample which is accommodated in one of theaccommodating regions 40 and which is to be used for the nextmeasurement arrives at the take-out position 40a. In order to preventthe liquid samples accommodated in the accommodating regions 40 fromevaporating and deteriorating, a cover (not shown) is provided on theaccommodating regions 40 outside of the take-out position 40a.

The centrifugation means 6 accommodates body fluid in accommodatingregions 42 and centrifuges it. Thereafter, as in the case of the sampleaccommodating means 4, the accommodating regions 42 are rotated untilthe liquid sample is located at the take-out position 42a in thesequence of take-out by the sample application means 5. By way ofexample, the body fluid is blood (whole blood). Upon centrifugation ofthe whole blood, blood plasma is separated up, and blood clot sediments.In this case, blood serum or blood plasma as the liquid sample can betaken up by the sample application means 5 without being separated intoa vessel different from the vessel of blood clot. As in the case of thesample accommodating means 4, a cover (not shown) is provided on theaccommodating regions 42 of the centrifugation means 6.

The sample application means 5 is moved by the movement means 17 in theextending direction of the rail 16, takes up the liquid sample from thetake-out position 40a or the take-out position 42a, and applies it tothe sample applying position 41 or 41' on the test film. Both the liquidsample and a reference solution should be applied to the electrolytedetermination slide, and therefore the sample applying positions 41' and41" are provided. The liquid sample is applied to the sample applyingposition 41', and the reference solution is applied to the sampleapplying position 41".

FIG. 3 is a sectional view taken along line 3--3 of FIG. 2. In FIG. 3,similar elements are numbered with the same reference numerals withrespect to FIGS. 1 and 2. With reference to FIG. 3, the long test film 3is accommodated in the film feed cassette 7 and the film wind-upcassette 8 and is accommodated in this form in the apparatus 1. The filmfeed cassette 7 is accommodated in a refrigerator 50 which constitutesthe test film accommodating means 12, and the film wind-up cassette 8 isaccommodated in a wind-up chamber 51.

With the configuration wherein the unused portion of the long test film3 is accommodated in the film feed cassette 7, the unused long test film3 can be accommodated in the test film accommodating means 12 withoutthe hands of the operator contacting the unused long test film 3.

As mentioned above, by way of example, the bar code 9 indicating the lotnumber, film number, measurement item, working life and otherinformation on the long test film 3 is provided on one face of the filmwind-up cassette 8. The information indicated by the bar code 9 is readby a bar code reading means 52 provided at a position in the wind-upchamber 51 corresponding to the position at which the bar code 9 islocated when the film wind-up cassette 8 is accommodated in the wind-upchamber 51. The information thus read is stored on, for example, thefloppy disk in the floppy disk drive unit 25 shown in FIG. 1, and isused for control of the measurement item and control of the length ofthe unused film portion remaining in the film feed cassette 7, andelimination of measurement errors caused by fluctuations amongproduction lots of the long test films 3. Also, in the case where thelong test film 3 is taken out of the apparatus 1 after being usedpartially, the film number, the length of the remaining unused filmportion and other information on the long test film 3 are stored on thefloppy disk unless a deletion command is entered from the keyboard 22shown in FIG. 1 or until the information is deleted automatically at thetime the long test film 3 runs out of the working life. When the longtest film 3 is again accommodated in the test film accommodating means12 for reuse, the film number of the long test film 3 is compared withthe information stored on the floppy disk, and the length of theremaining unused portion of the long test film 3 and other items arecontrolled again.

The aforesaid bar code 9 may be provided on the film feed cassette 7,and the bar code reading means 52 may be provided inside of therefrigerator 50. Also, the means for transmitting the lot number, theworking life and other information on the long test film 3 to theapparatus 1 is not limited to the bar code 9 and the means for readingthe bar code 9, and any other known means for recording the informationon the film feed cassette 7 or on the film wind-up cassette 8 andreading the information at the time the long test film 3 is accommodatedin the apparatus 1 may be employed for this purpose.

The refrigerator 50 is enclosed by a refrigerator wall 54 composed of aheat insulating material. A cooling and dehumidifying device 58 forkeeping the inside of the refrigerator 50 at a predetermined lowtemperature and low humidity is provided on one surface of therefrigerator wall 54, and air inside of the refrigerator 50 iscirculated by a fan 60.

FIG. 4 shows the rates of deterioration of the unused long test film 3with the passage of time when the unused long test film 3 is maintainedunder various temperature-humidity conditions, in terms of the number ofdays for which the long test film 3 can be stored under such conditionswithout becoming unusable for measurement. Each of the numeralsindicated in the circles in FIG. 4 represents the number of days forwhich the long test film 3 can be stored under the temperature-humidityconditions corresponding to the circle without becoming unusable formeasurement. The number of days for which the long test film 3 can bestored under the temperature-humidity conditions without becomingunusable for measurement increases sharply at the left bottom of thegraph (under a low temperature, low humidity conditions) shown in FIG.4. Therefore, the long test film 3 can be stored for a longer period inthe apparatus 1 by accommodating the unused portion of the long testfilm 3 in the refrigerator 50 and maintaining the unused portion at apredetermined low temperature and low humidity adjusted by consideringthe working life and the working frequency of the long test film 3 andother items.

Reverting to FIG. 3, when the film wind-up cassette 8 is accommodated inthe wind-up chamber 51, a rotation shaft of a test film wind-up motor 53constituting the test film conveyance means for the long test film 3provided in the wind-up chamber 51 engages with a hole 11 formed at thecenter of a reel 10 of the film wind-up cassette 8. As the motor 53 isrotated, the long test film 3 is pulled out of the film feed cassette 7through a film outlet 49 of the refrigerator 50, and is wound up in thefilm wind-up cassette 8. As mentioned above, the film feed cassette 7and the film wind-up cassette 8 are provided independently of eachother. Therefore, the film outlet 49 of the refrigerator 50 may be assmall as to allow the passage of the long test film 3 therethrough, andthe cooling and dehumidifying efficiency in the refrigerator 50 can bemaintained high. Also, the long test film 3 can also be used in variousapparatuses among which the distance between the refrigerator 50 and thewind-up chamber 51 differs. Furthermore, with the configuration whereinthe used portion of the long test film 3 is accommodated in the filmwind-up cassette 8, the used long test film 3 on which the liquid samplehas already been applied can be taken out of the apparatus 1 anddiscarded or processed for other purposes without the hands of theoperator contacting the used long test film 3. For discarding the usedlong test film 3, a cutter for cutting the used film may be providednear the inlet of the wind-up chamber 51, and a box for receiving thecut film fragments and capable of being fitted to and removed from theapparatus 1 may be provided instead of the wind-up chamber 51. With thisconfiguration, the used film contained in the box can be taken out ofthe apparatus 1 together with the box and discarded or processed forother purposes without the hands of the operator contacting the usedfilm. In this case, conveyance of the test film may be carried out bythe provision of conveying rollers for grasping and conveying the testfilm.

The exposed portion of the long test film 3 between the film feedcassette 7 and the film wind-up cassette 8 passes through an incubator55 provided with a shutter 54 and between a light projector and a lightreceiver of a photoelectric switch 56. A measuring device 57 formeasuring the optical density produced by a color reaction of the longtest film 3 with the liquid sample is disposed under the incubator 55.

With the configuration illustrated in FIG. 3 wherein the refrigerator 50and the incubator 55 are close to each other, the length of the portionof the long test film 3 pulled out of the film feed cassette 7 for asingle measurement may be short so that more measurements can beachieved with the long test film 3 of the same length.

With reference to FIG. 5 illustrating the configuration of the incubator55 along line 5--5' of FIG. 3, the long test film 3 is pulled out of thefilm feed cassette 7 and intermittently moved from the rear of thedrawing sheet in FIG. 5 to the front thereof. Prior to this step, anupper cover 55a of the incubator 55 has been moved in the direction asindicated by the arrow A. After the long test film 3 has been moved asmentioned above, the upper cover 55a is moved in the direction asindicated by the arrow B, and pushes down the long test film 3 asillustrated. Then, the shutter 54 is moved in the direction as indicatedby the arrow C, the sample application means 5 is moved down to applythe liquid sample from the sample applying nozzle 15 onto the long testfilm 3 through a hole 59. Thereafter, the shutter 54 is moved in thedirection as indicated by the arrow D to close the hole 59 asillustrated and prevent air flow between the inside and outside of thehole 59, and the incubator 55 incubates so that the temperature in theinside thereof reaches a predetermined value, for example, 37° C. In thecourse of the incubation or after the incubation is finished, theoptical density at the portion of the long test film 3 on which theliquid sample has already been applied is measured by the measuringdevice 57. Instead of providing the shutter 54, the upper cover 55a ofthe incubator 55 may be constituted moveable in the directions asindicated by the arrows C and D as well as in the directions asindicated by the arrows A and B. In this case, the upper cover 55a ofthe incubator 55 need not be provided with the hole 59 for sampleapplication. But instead, after the liquid sample has been applied ontothe long test film 3 by moving the upper cover 55a in the direction asindicated by the arrow C, the upper cover 55a may be moved to itsoriginal position in the direction as indicated by the arrow D, andincubation may then be carried out.

With this embodiment wherein the sample application, incubation andmeasurement are carried out at a single position, the position to whichthe liquid sample has been applied is incubated and measured reliablyeven though the accuracy of feed of the long test film 3 by the testfilm wind-up motor 53 is low. Also, since the sample applying position41 (as shown in FIG. 2) with respect to the incubator 55 is alwaysconstant, the temperature distribution inside of the incubator 55 isconstant, the color reaction is effected under constant conditions, andthe measurement accuracy becomes high. Furthermore, in the case wherethe sample application, incubation and measurement are carried out atdifferent positions, it is necessary for the rotation of the motor 53 tobe controlled each time the long test film 3 is to be moved from thesample applying position to the incubating position or from theincubating position to the measuring position. However, with theaforesaid embodiment wherein the sample application, incubation andmeasurement are carried out at a single position, such complicatedcontrol is not required.

The photoelectric switch 56 shown in FIG. 3 detects holes or marks ofthe long test film 3. Based on the signal generated by the photoelectricswitch 56, the long test film 3 is pulled out of the film feed cassette7 by a length necessary for a single measurement. The computer 20 shownin FIG. 1 counts the number of pull-out operations of the long test film3, and issues a warning, for example, by sound or light, to the operatorwhen the length of the remaining unused portion of the long test film 3has decreased to a predetermined value or less. Also, a hole or a markdiscriminable by the photoelectric switch 56 from the holes or marksprovided at the predetermined measurement length intervals on the longtest film 3 is provided near the tail edge portion of the long test film3. When the hole or mark near the tail edge portion of the long testfilm 3 is detected, the photoelectric switch 56 produces a signal forstopping the pull-out of the long test film 3. The end of the long testfilm 3 may be judged on the basis of only the value counted by thecomputer 20. However, the end mark or the like should preferably beprovided on the long test film 3 itself to cope with the case whereinthe long test film 3 is taken out of the apparatus 1 after it haspartially been used for measurement, and is artificially wound upslightly and then loaded to the apparatus 1 again.

An elongated pipe 43 continuing into a leading end 15a of the sampleapplying nozzle 15 is provided in the sample application means 5. Thepipe 43 is communicated with a flexible pipe 44 so that the liquidsample is fed through the pipes 43 and 44 into the sample applicationmeans 5 and applied onto the test film as will be described later. Thereference solution is fed and washing liquid is delivered through thepipes 43 and 44.

A liquid level detector 45 is provided in parallel with the sampleapplying nozzle 15 in the vicinity thereof. The liquid level detector 45is provided so that its leading edge 45a is slightly (for example, byapproximately 2.5 mm) higher than the leading edge 15a of the sampleapplying nozzle 15. When the sample application means 5 is moved down bythe movement means 17 for taking up the liquid sample accommodated inthe sample accommodating means 4 or the centrifugation means 6, theleading edge 15a of the sample applying nozzle 15 enters the liquidsample, and the leading edge 45a of the liquid level detector 45contacts the liquid sample. At this time, a signal indicating that theleading edge 45a of the liquid level detector 45 has contacted theliquid sample is produced by the liquid level detector 45, andtransmitted to the circuit region 19 shown in FIG. 1 through a signalline 46. Based on the signal, the downward movement of the sampleapplication means 5 is stopped. In this manner, the leading edge 15a ofthe sample applying nozzle 15 can be entered into the liquid sample upto a predetermined depth from the surface of the liquid sampleregardless of the amount of the liquid sample.

With reference to FIG. 6 illustrating the configuration of theelectrolyte determination slide accommodating region 14 along line 6--6of FIG. 2, electrolyte determination slides 30 are stacked in a slidemagazine 61, and a bottom plate 63 of the slide magazine 61 is urged upby a spring 62. The top slide 30' among the electrolyte determinationslides 30 is pushed up against a top plate 64 of the slide magazine 61.A slide conveying member 65 constituting the test film conveyance meansfor the slides 30 is moveable by a drive means (not shown) in thedirections as indicated by the arrows E and F. As the slide conveyingmember 65 is moved in the direction as indicated by the arrow E, aleading edge 65a thereof enters a slit 66 formed in the slide magazine61, and pushes the top slide 30' in the slide magazine 61. As a result,the slide 30' is pushed out of the slide magazine 61 through a slit 66'into an incubator 68 as indicated by a reference numeral 30". At theincubator 68, a shutter 69 is opened, a sample liquid is applied to theslide 30", the shutter 69 is then closed, and the slide 30" isincubated. Thereafter, a measuring device 70 is moved up in thedirection as indicated by the arrow G until potential measuring probes67 contact electrodes (not shown) of the slide 30" in the incubator 68,and a difference in potential is measured. Thereafter, the measuringdevice 70 is moved in the direction as indicated by the arrow H to itswaiting position as shown in FIG. 6. The incubator 68 has nearly thesame configuration as the incubator 55 for the long test film 3 shown inFIG. 5, except that the slide 30' pushed out by the slide conveyingmember 65 can be accommodated as the slide 30", and the liquid sampleand the reference solution can be applied to the predetermined positionson the slide 30". Also, instead of providing the measuring device 57shown in FIG. 5, the probes 67 of the measuring device 70 moved in thedirection as indicated by the arrow G in FIG. 6 contact thepredetermined electrodes to measure a difference in potential.

As in the case of the long test film 3, instead of providing the shutter69, the effect of the shutter 69 may be achieved by an upper cover 68aof the incubator 68. Also, since the sample application, incubation andmeasurement are carried out at a single position, the same effects as inthe case of the long test film 3, such as simplification of the controlof push-out of the slide 30' by the slide conveying member 65 andimproved measurement accuracy, can be obtained.

After the measurement is finished, the slide 30" is pushed by the slideconveying member 65 leftward in FIG. 6 into a slide discarding region71. The slide conveying member 65 is then moved in the direction asindicated by the arrow F to the waiting position shown in FIG. 6.

As the slides 30 are pushed one by one out of the slide magazine 61, thebottom plate 63 of the slide magazine 61 is pushed up by the spring 62.At the time a protrusion 63a projecting from the bottom plate 63 out ofthe slide magazine 61 faces a proximity switch 72, a warning is issuedto the operator to instruct replenishment of slides 30. In the casewhere a predetermined number of the slides 30 are then pushed out of theslide magazine without new slides replenished and the slide magazine 61runs out of the slide 30 while the liquid sample to be measured for adifference in potential is still present, the apparatus 1 is stoppedwithout sample application and other operations for measurement of theliquid sample being carried out.

With reference to FIG. 7 illustrating the sample accommodating means 4and the centrifugation means 6 along line 7--7 of FIG. 2, the sampleaccommodating means 4 is constituted so that sample cups 80 forcontaining the liquid samples are placed in the accommodating regions 40provided in the ring-like area on the upper surface of the sampleaccommodating means 4, and the overall sample accommodating means 4 isrotated by a motor 81 via gears 82, 82' and 82". The operation of themotor 81 is controlled so that the liquid samples are located one afteranother at the liquid sample take-out position 40a shown in FIG. 2 inthe sequence of take-out from the sample accommodating means 4 andsample application.

Sample cups 80' containing body fluid are placed in the accommodatingregions 42 on the upper surface of the centrifugation means 6. From theviewpoint of cup control and reduction in cost, cups of the same type asthe sample cups 80 on the sample accommodating means 4 are employed asthe sample cup 80'.

A motor 83 is provided for centrifugation. A motor 85 rotates the samplecups 80', to locate the liquid sample (body fluid) after centrifugationat the liquid sample take-out position 42a shown in FIG. 2 as in thecase of the motor 81.

At the time centrifugation is to be carried out, a clutch 86 isdisengaged to disconnect the motor 85 from a rotation shaft 87, and aclutch is engaged to transmit the power of the motor 83 to the rotationshaft 87. The motor is operated in this condition to rotate the samplecups 80' at a high speed with the bottoms of the sample cups 80' facingoutward and openings thereof facing inward by the centrifugal force sothat the body fluid does not spill out of the sample cups 80', 80', . .. After centrifugation is thus carried out for a predetermined time, theclutch 84 is disengaged to disconnect the motor 83 from the rotationshaft 87, and the clutch 86 is engaged to connect the motor 85 to therotation shaft 87. The motor 85 is then operated to rotate the samplecups 80' until the liquid sample (body fluid) after centrifugation islocated at the liquid sample take-out position 42a shown in FIG. 2.

As the centrifugation means 6 is provided in the space inward from thesample accommodating means 4, the overall apparatus 1 can be made small.Also, since the accommodating regions 42 of the centrifugation means 6are provided inward from the accommodating regions 40 arranged in thering-like area of the sample accommodating means 4, feed of the liquidsample (body fluid) to the apparatus 1 for measurement can be carriedout at a single position, and therefore a high operating efficiency canbe obtained.

With reference to FIG. 8 showing the pipes communicating with the pipe43 passing through the center of the sample applying nozzle 15 of thesample application means 5, the pipe 43 communicates with the flexiblepipe 44 which communicates with an end of a pipe 90. The pipe 90communicates at its intermediate point with a pipe 93 communicating witha space 98 in a cylinder 97 of a suction and delivery means 96, and theother end of the pipe 90 is connected to a port 100 of a solenoid valve99. A pipe 91 connects a port 101 of the solenoid valve 99 with a port104 of a solenoid valve 103. A port 102 of the solenoid valve 99 isconnected to a pipe 94 communicating with a space 109 in a cylinder 108of a suction and delivery means 107. The solenoid valve 99 is changedover by a signal received from the exterior to communicate the pipes 90and 94 with each other and disconnect the pipe 91 from the pipe 94, orconversely to communicate the pipes 91 and 94 with each other anddisconnect the pipe 90 from the pipe 94. A port 106 of the solenoidvalve 103 is connected to an end of a pipe 95 having the other endextending to the vicinity of the bottom of a tank 111 via an opening111a of the tank 111 and immersed in a reference solution 110 in thetank 111. A liquid level detector 112 is provided in the tank 111 fordetecting the level of the reference solution 110 in the tank 111. Asignal indicating the level of the reference solution 110 is transmittedto the circuit region 19 shown in FIG. 1 via a signal line (not shown),and a warning is issued by, for example, sound or light, to the operatorwhen the level of the reference solution 110 is low. A port 105 of thesolenoid valve 103 is connected to an end of a pipe 92 having the otherend extending to the vicinity of the bottom of a tank 114 via an opening114a of the tank 114 and immersed in a washing liquid 113 in the tank114. As in the case of the tank 111, a liquid level detector 115 isprovided in the tank 114. The solenoid valve 103 is changed over by asignal received from the exterior to communicate the pipes 91 and 92with each other and disconnect the pipe 91 from the pipe 95, orconversely to communicate the pipes 91 and 95 with each other anddisconnect the pipe 91 from the pipe 92.

The suction and delivery means 96 sucks the liquid sample from theleading edge 15a of the sample applying nozzle 15, and applies ittherefrom onto the test film. In order to suck the liquid sample, theleading edge 15a of the sample applying nozzle 15 is entered into theliquid sample accommodated in the sample accommodating means 4 or thecentrifugation means 6 until the leading edge 45a of the liquid leveldetector 45 contacts the surface of the liquid sample, and the solenoidvalve 99 is controlled so that the pipes 90 and 94 disconnect from eachother and the pipes 91 and 94 communicate with each other. In thiscondition, the motor 116 is rotated in the direction as indicated by thearrow I, the rotation force is converted into linear motion via a camplate 117 and a link mechanism 118, and the linear motion is transmittedto a piston rod 119. As a result, the piston rod 119 is moved down topull a piston 124 down and broaden a space 98 inside of the cylinder 97.In this manner, the liquid sample is moved from the leading edge 15a ofthe sample applying nozzle 15 to the pipes 43, 44 and 90. The sampleapplication means 5 is constituted to be capable of accommodating theliquid sample, at one time, in an amount necessary for achieving thesample application sequentially to a plurality of the long test films,which contain the reagents different in accordance with the measurementitems and which are accommodated in the test film accommodating means12. In order to apply the liquid sample onto the test film, the sampleapplication means 5 is moved to the sample applying position of the testfilm, the shutter 54 or the shutter 69 is opened, the sample applyingnozzle 15 is moved down, and then the motor 116 is rotated in thedirection as indicated by the arrow J. As a result, the drive force ofthe motor 116 is transmitted to the piston rod 119 via the cam plate 117and the link mechanism 118, the piston rod 119 is moved up to push thepiston 124 up, and the liquid sample is applied in an amountcorresponding to the extent of the movement of the piston 124.

In order to deliver the reference solution 110 from the leading edge 15aof the sample applying nozzle 15, the solenoid valve 99 is firstcontrolled so that the pipes 91 and 94 communicate with each other andthe pipes 90 and 94 are disconnected from each other, and the solenoidvalve 103 is controlled so that the pipes 91 and 95 communicate witheach other and the pipes 91 and 92 are disconnected from each other. Inthis condition, the motor 120 is rotated in the direction as indicatedby the arrow K, the rotation force is converted into linear motion via acam plate 121 and a link mechanism 122, and the linear motion istransmitted to a piston rod 123. As a result, the piston rod 123 ismoved down to pull a piston 125 down and broaden a space 109 inside ofthe cylinder 108. In this manner, the reference solution 110 is movedthrough the pipe 95, the solenoid valve 103, the pipe 91, the solenoidvalve 99 and the pipe 94 into the space 109 in the cylinder 108. Then,the solenoid valve 99 is controlled so that the pipes 90 and 94communicate with each other and the pipes 91 and 94 are disconnectedfrom each other. Thereafter, the motor 120 is rotated in the directionas indicated by the arrow L to move the piston rod 123 up and push thepiston 125 up, and the reference solution 110 is delivered from theleading edge 15a of the sample applying nozzle 15 in an amountcorresponding to the extent of movement of the piston 125.

Delivery of the washing liquid 113 from the leading edge 15a of thesample applying nozzle 15 is controlled in the same manner as thedelivery of the reference solution 110, except that the solenoid valve103 is controlled so that the pipes 91 and 92 communicate with eachother and the pipes 91 and 95 are disconnected from each other when thewashing liquid 113 is to be moved to the space 109 in the cylinder 108.

With the aforesaid pipe connections, the sample applying nozzle 15 worksfor both the liquid sample and the reference solution, and it is notnecessary to use dual nozzles as disclosed in, for example, JapaneseUnexamined Patent Publication No. 61(1986)-173131. With this embodimentwherein a single nozzle is used, the mechanism is simplified, operationfailures decrease, and the cost decreases.

Also, with the aforesaid embodiment wherein the opening 111a of the tank111 containing the reference solution 110 is made as small as to allowinsertion of the pipe 95 thereinto, evaporation and deterioration of thereference solution 110 can be prevented as compared with the case wherethe reference solution 110 is kept to stand in the sample cups 80 at theaccommodating regions 40 as in the case of the liquid sample.Furthermore, with the substantially large tank 111, no replenishment ofthe reference solution 110 thereto is required for a long period.

Operations of the embodiment the biochemical analysis apparatus inaccordance with the present invention shown in FIG. 1 will be describedhereinbelow. It is ordinarily practiced that a monitor means formonitoring the operating condition is provided on the apparatus 1,thereby automatically carrying out processing such as stop of theapparatus 1 and issuance of a warning to the operator in the case ofabnormal operation. Therefore, processing in the case of abnormaloperation will be only briefly described below.

First, the power source switch of the apparatus 1 is turned on by theoperator to supply electric power to the apparatus 1 only after thenecessary test film has been accommodated in the apparatus 1. In thecase where the power switch is off and the test film is present in thetest film accommodating means 12, the cooling and dehumidifying device58 is kept energized to maintain the inside of the refrigerator 50 at apredetermined temperature and humidity.

After the electric power is supplied to the apparatus 1, initial settingof the apparatus 1 is carried out in the sequence described below.Specifically, in the case where the sample application means 5 is not atits upper position, it is moved to its upper position by the movementmeans 17. The sample application means 5 is then moved by the movementmeans 17 to a predetermined end of the rail 16.

Thereafter, the sample application means 5 is moved by the movementmeans 17 toward the washing region 18, and is stopped by a signalreceived from a position detection means (not shown) for producing thesignal at the time the sample application means 5 arrives at the washingregion 18. On the other hand, by way of example, a pulse encoder (notshown) is provided on a shaft of a motor (not shown) for moving thesample application means 5 along the rail 16. The pulses produced by thepulse encoder in proportion to the amount of rotation of the motor arecounted during the movement of the sample application means 5 from thepredetermined end of the rail 16 to the washing region 18. Based on thenumber of the pulses counted, the presence or absence of slippingbetween the shaft of the motor and the movement of the sampleapplication means 5 along the rail 16 is detected.

The positions of the pistons 124 and 125 shown in FIG. 8 are monitoredto detect whether they are or are not at their start positions that makethe space 98 and the space 109 smallest. In the case where the pistons124 and 125 are not at their start positions, the motors 116 and 120 arerotated in the directions as indicated by the arrows J and L,respectively, to move the pistons 124 and 125 to their start positions.At this time, the solenoid valve 99 is controlled so that the pipes 90and 94 communicate with each other. In the case where there has beenliquid remaining in, for example, the space 109 in the cylinder 108, theliquid is delivered from the leading edge 15a of the sample applyingnozzle 15 to the washing region 18 via the pipe 43.

The shutter 54 shown in FIG. 3 and the shutter 69 shown in FIG. 6 aremonitored to detect whether they are present at the positions closingthe incubators 55 and 68, and the inside of the incubator 55 and theinside of the incubator 68 are maintained at the predeterminedtemperature.

Also, monitor is effected to detect whether, for example, the levels ofthe reference solution 110 and the washing liquid 113 in the tanks 111and 114 are or are not higher than the predetermined levels, and whetherthe measuring device 70 and the slide conveyance means 65 are or are notat their waiting positions. Then, issuance of a warning to the operatorwhen necessary and automatic shifting to the initial condition arecarried out.

After the apparatus 1 has been set to the initial condition in themanner described above, the completion of the initial setting isindicated to the operator.

Thereafter, the operator pours the liquid sample which need not becentrifuged into the sample cup 80 and places it at a predeterminedposition in the sample accommodating means 4. Body fluid requiringcentrifugation is poured into the sample cup 80', and the sample cup 80'is placed at a predetermined position in the centrifugation means 6. Theinformation on the measuring item for the liquid sample (body fluid) isentered from the keyboard 22 or from a floppy disk storing theinformation inserted into the floppy disk drive unit 25. The apparatus 1automatically detects whether the test film corresponding to themeasuring item thus specified has been or has not been accommodated inthe test film accommodating means 12. Also, the position of the liquidsample (body fluid) in the sample accommodating means 4 (centrifugationmeans 6) is entered to the apparatus 1 from, for example, the keyboard22. In the case where measurement is to be carried out for a pluralityof the liquid samples (body fluids), the aforesaid operations arerepeated.

Thereafter, a measurement start instruction is given by the operator tothe apparatus 1 by use of, for example, the keyboard 22, and theautomatic measuring operations are started.

First, in the case where the body fluid samples have been accommodatedat the centrifugation means 6, centrifugation is carried out by theoperations of the motors 83, 85 and the clutches 84, 86. After thecentrifugation, the body liquid samples (liquid samples) are located oneafter another at the liquid sample take-out position 42a in the sequenceof measurement.

In the case where the liquid samples have been accommodated at thesample accommodating means 4, they are located one after another at theliquid sample take-out position 40a in the sequence of measurement.

Thereafter, the sample application means 5 positioned at the washingregion 18 in the initial condition is moved to suck the liquid samplefrom the sample accommodating means 4 or the centrifugation means 6 intothe pipes 43, 44 and 90 by broadening the space 98 in the cylinder 97while the level of the liquid sample is monitored by means of the liquidlevel detector 45. In the case where a plurality of measurements are tobe carried out, in order to complete suction of the liquid sample by asingle operation and shorten the overall measurement time, the liquidsample is sucked in an amount sufficient for all measurements. At thistime, the pipes 43, 44 and 90 have often been filled with the washingliquid by the washing operation as will be described later. Therefore,before the liquid sample is thus sucked, air is slightly sucked into thepipe 43 with the leading edge 15a of the sample applying nozzle 15present in air, and the leading edge 15a of the sample applying nozzle15 is then entered into the liquid sample. As a result, an air layerintervenes between the washing liquid and the sucked liquid sample sothat they do not mix together.

Then, the sample application means 5 is moved up and moved along therail 16 to the sample applying position on the test film specified inadvance. The case where the liquid sample is applied onto the long testfilm 3 and the case where it is applied onto the slide 30 willhereinbelow be described separately.

First, in the case where the liquid sample is to be applied to the longtest film 3, sample application to the long test film 3 is first carriedout even though sample application to the slide 30 is necessary, therebyto shorten the overall measurement time. As described above withreference to FIG. 5, sample application to the long test film 3 iscarried out by the operations of the shutter 54 and the upper cover 55aof the incubator 55. In order to minimize deterioration of the long testfilm 3 with the passage of time, the long test film 3 is pulled out ofthe film feed cassette 7 by the test film conveyance means exactly priorto the sample application.

In the case where the liquid sample is to be applied to a plurality ofthe long test films 3 in order to minimize the movement of the sampleapplication means 5 and shorten the overall measurement time, the sampleapplication is basically carried out sequentially from the long testfilm 3 accommodated at an end among the long test films 3 toward the oneat the other end. However, in the case where the measurement sequence isspecified by the operator when, for example, measurement results of ameasurement item are to be investigated urgently, the sample applicationis carried out in the specified sequence.

After the liquid sample has been applied to the long test film 3, thelong test film 3 is incubated, and the optical density at the portionapplied with the liquid sample is measured. The measurement results arefed to the computer 20, necessary calculation processing is carried out,and the results of calculation processing are stored and fed out.

Sample application to the slide 30, when necessary, is carried out asdescribed below.

In the case where sample application is to be carried out for both theslide 30 and the long test film 3, sample application to the long testfilm 3 is first carried out in the manner as mentioned above, and thenthe sample application means 5 is moved to the sample applying position41' of the slide 30, and the liquid sample is applied to the slide 30 inthe manner as mentioned above. As in the case of the long test film 3,in order to prevent deterioration of the slide 30, conveyance of theslide 30 from the refrigerator 50 to the predetermined position by theslide conveyance member 65 is carried out exactly prior to the sampleapplication to the slide 30. After the liquid sample has been applied tothe slide 30, the sample application means 5 is moved to the nozzlewashing region 18. A small vessel (not shown) is placed at the nozzlewashing region 18. By way of example, distilled water is contained inthe vessel and is made to run so that fresh distilled water is alwayscontained in the vessel. After being moved to the nozzle washing region18, the sample application means 5 is moved down by the movement means17 until the leading edge 15a of the sample applying nozzle 15 entersthe distilled water.

During the movement of the sample application means 5, the referencesolution 110 is accumulated in the cylinder 108 shown in FIG. 8 by theabove-mentioned operations. After the leading edge 15a of the sampleapplying nozzle 15 has been entered to the distilled water, the liquidsample remaining in the pipe 43 and other pipes is delivered from theleading edge 15a of the sample applying nozzle 15. In the case where thepipe 90 and other pipes have been filled with the washing liquid, thewashing liquid is then delivered. Also, the reference solution 110 whichhas slightly been mixed with the washing liquid in the pipe 90 and otherpipes is delivered. As a result, the reference solution 110 is filled inthe pipes up to the leading edge 15a of the sample applying nozzle 15.

The reference solution 110 is then applied to the predetermined positionon the slide 30. The reference solution 110 should be applied to theslide 30 as early as possible (for example, within 3 seconds) after theliquid sample has been applied to the slide 30, and therefore theapplication of the liquid sample to the slide 30 is carried out afterthe sample application to the necessary long test film 3 has beenfinished. With this procedure, when sample application is necessary forboth the long test film 3 and the slide 30, take-out of the liquidsample from the sample accommodating means 4 or the centrifugation means6 can be completed by a single operation, and the overall measurementtime can be shortened. The measurement time for the slide 30 (Na⁺, K⁺,Cl⁻ potential difference measurement item) is approximately one minute,whereas the measurement time for the long test film 3 (color reaction)is approximately four minutes on the average. Therefore, in order toshorten the overall measurement time, measurement for the slide 30should be carried out last. Also, since the sample applying positions41' and 41" for the slide 30, the nozzle washing region 18, and thesample accommodating means 4 are provided close to one another, thedistance of movement of the sample application means 5 between the stepof application of the liquid sample to the slide 30 and the step ofapplication of the reference solution to the slide 30 by the aforesaidoperations can be minimized, and the overall measurement time canfurther be shortened.

The slide 30 on which the liquid sample and the reference solution havealready been applied is incubated in the manner as mentioned above, andthe difference in potential is measured. The measurement results are fedto the computer 20, necessary calculation processing is carried out, andthe results of calculation processing are stored and fed out.

After the sample application is finished in the manner as mentionedabove, the sample application means 5 is moved to the nozzle washingregion 18, and the leading edge 15a of the sample applying nozzle 15 isimmersed in distilled water. Thereafter, the pistons 124 and 125 shownin FIG. 8 are moved to their start positions if they were not there, andthe liquid sample, the reference solution and the like are deliveredfrom the leading edge 15a of the sample applying nozzle 15. The washingliquid is then accumulated in the cylinder 108 by the above-mentionedoperations, and delivered from the leading edge 15a of the sampleapplying nozzle 15 for the purpose of washing.

In the case where the liquid sample which is to be determined next isstill present in the sample accommodating means 4 or the centrifugationmeans 6 after the aforesaid operations have been finished, the liquidsample is moved to the liquid sample take-out position 40a or 42a, andthe aforesaid operations are repeated.

FIG. 9 shows another embodiment of the biochemical analysis apparatus inaccordance with the present invention.

With reference to FIG. 9, a biochemical analysis apparatus 1' isdifferent from the aforesaid apparatus 1 in that a sample applyingnozzle 15' of a sample application means 5' is moveable along a circulararc path indicated by the chain line in FIG. 9. Sample applyingpositions 201, 201' and 202" for all test films pulled or pushed out ofa test film accommodating means 12', a liquid sample take-out position202 of the sample accommodating means 4, and a liquid sample take-outposition 203 of the centrifugation means 6 are disposed in the circulararc path.

With the arrangement in the circular arc path, as in the case of theaforesaid embodiment employing the arrangement on the straight line, theconfiguration of a movement means (not shown) for rotating the sampleapplication means 5' can be simplified, failures of the apparatus 1' canbe minimized, and the cost thereof can be reduced.

FIG. 10 shows a sample accommodating means 4' provided with thecentrifuging function.

In the aforesaid embodiment, as shown in FIG. 7, the sampleaccommodating means 4 is disposed outward from the centrifugation means6. Instead, in the embodiment shown in FIG. 10, the sample accommodatingmeans 4' accommodates both the liquid sample and the body fluid, and isprovided with the centrifuging function for preparing the liquid sampleby centrifuging the body fluid accommodated in the sample accommodatingmeans 4'. In FIG. 10, similar elements are numbered with the samereference numerals with respect to FIG. 7. With this embodiment, theconfiguration becomes simpler, failures of the apparatus can bedecreased to a higher extent and the cost thereof can further be reducedthan in the case where the sample accommodating means 4 and thecentrifugation means 6 are disposed as shown in FIG. 7.

FIG. 11 shows a further embodiment of the biochemical analysis apparatusin accordance with the present invention. In this embodiment, instead ofproviding a centrifugation means 6' inward from the sample accommodatingmeans 4, an apparatus 1' is constituted so that it is dividable into ananalysis unit 204 and a centrifugation unit 205.

By way of example, the analysis unit 204 and the centrifugation unit 205stand side by side as shown in FIG. 11, the body fluid aftercentrifugation (liquid sample) is transferred by a sample transfer means206 from the centrifugation means 6' to the sample accommodating means4. Transfer of the liquid sample may be carried out by taking up theliquid sample by use of the same configuration as the sample applicationmeans 5. Alternatively, sample cups of the same type for containing theliquid sample (body fluid) may be used at the centrifugation means 6'and the sample accommodating means 4, and the liquid sample may betransferred together with the sample cup from the centrifugation means6' to the sample accommodating means 4.

After the liquid sample has been transferred as mentioned above,measurement is carried out in the same manner as in the case where noliquid sample (body fluid) is placed at the centrifugation means 6 inthe aforesaid embodiment.

With the apparatus 1" dividable into the analysis unit 204 and thecentrifugation unit 205, in the case where only a liquid samplerequiring no centrifugation is to be analyzed or a centrifugal separatoris already present, analysis can be carried out by use of the analysisunit 204 alone. Therefore, the apparatus 1" is advantageous from theviewpoint of economics. In the case where the centrifugation unit 205 isprovided as shown in FIG. 11, the analysis unit 204 and thecentrifugation unit 205 can be operated integrally by the aid of thesample transfer means 206.

The aforesaid embodiments of the biochemical analysis apparatus inaccordance with the present invention are constituted for carrying outboth the measurement of a change in the optical density by use of thelong test film 3 and the measurement of a difference in potential by useof the slide. However, the function of measuring the difference inpotential may be provided when necessary, and the biochemical analysisapparatus may be constituted for carrying out only the measurement of achange in the optical density by use of the long test film 3.

It is also possible to constitute the biochemical analysis apparatus forcarrying out one of the measurement of a change in the optical densityby use of the long test film 3 and the measurement of a difference inpotential by use of the slide. Also, in the case where the biochemicalanalysis apparatus is constituted for carrying out the measurement of achange in optical density, a slide type test film may be employedinstead of the long test film 3.

Also, in the aforesaid embodiments, a plurality of items can be measuredby accommodating a plurality of the long test films 3. The biochemicalanalysis apparatus in accordance with the present invention may also beconstituted for accommodating only a single long test film 3.

We claim:
 1. A biochemical analysis apparatus comprising:i) a sampleholding means for holding a liquid sample, ii) a centrifugation meansfor receipt of body fluid and preparing a liquid sample bycentrifugation of the body fluid, iii) a sample transfer means fortransferring said liquid sample prepared by said centrifugation means tosaid sample holding means, iv) a test film holding means for holding n aside-by-side arrangement a plurality of rolls of test film capable ofreacting with said liquid sample to result in a change, v) a test filmconveyance means for each of said rolls of test film for sequentiallyconveying the test film of a roll held in said test film holding meansto a predetermined position outside of said test film holding means, vi)a sample application means for taking up said liquid sample out of saidsample holding means and applying a predetermined amount of said liquidsample onto a said test film conveyed to said predetermined position,vii) an incubator for maintaining the sample-applied portion of saidtest film at said predetermined position at a predetermined temperaturefor a predetermined time, said incubator including an opening throughwhich said sample application means applies said liquid sample to saidtest film, and means for preventing air flow between a position insideof said incubator and a position outside of said incubator, said airflow preventing means being reciprocally movable to cover said opening,and viii) a detection means for measuring a change in optical density ofsaid sample-applied portion of said test film at said predeterminedposition based on a reaction product between said sample applied andsaid test film during or after the passage of said predetermined time,wherein said predetermined position is inside said incubator.
 2. Anapparatus as defined in claim 1 wherein said test film comprises anelongated tape.
 3. An apparatus as defined in claim 2 wherein said testfilm holding means is constituted to hold a plurality of elongatedtapes, said test film conveyance means, said incubator and saiddetection means are provided to correspond to each of a plurality ofsaid elongated tapes, and a movement means is provided for moving saidsample application means to carry out the sample application to thepredetermined position on each of a plurality of said elongated tapes.4. A biochemical analysis apparatus comprising:i) a sample holding meansfor holding a liquid sample, ii) a centrifugation means for receipt ofbody fluid and preparing a liquid sample by centrifugation of the bodyfluid, iii) a test film holding means for holding in a side-by-sidearrangement a plurality of rolls of test film capable of reacting withsaid liquid sample to result in a change, iv) a test film conveyancemeans for each of said rolls of test film for sequentially conveying thetest film of a roll held in said test film holding means to apredetermined position outside of said test film holding means, v) asample application means for taking up said liquid sample out of one ofsaid sample holding means and said centrifugation means selectively andapplying a predetermined amount of said liquid sample onto said testfilm conveyed to said predetermined position, vi) an incubator formaintaining the sample-applied portion of said test film at saidpredetermined position at a predetermined temperature for apredetermined time, said incubator including an opening through whichsaid sample application means applies said liquid sample to said testfilm, and means for preventing air flow between a position inside ofsaid incubator and a position outside of said incubator, said air flowpreventing means being reciprocally movable to cover said opening, andvii) a detection means for measuring a change in optical density of saidsample-applied portion of said test film situated at said predeterminedposition based on a reaction product between said sample applied andsaid test film during or after the passage of said predetermined time,wherein said predetermined position is inside said incubator.
 5. Anapparatus as defined in claim 4 wherein said test film comprises anelongated tape.
 6. An apparatus as defined in claim 5 wherein said testfilm holding means is constituted to hold a plurality of the elongatedtapes, said test film conveyance means, said incubator and saiddetection means are provided to correspond to each of a plurality ofsaid elongated tapes, and a movement means is provided for moving saidsample application means to carry out the sample application to thepredetermined position on each of a plurality o said elongated tapes. 7.An apparatus as defined in claim 4 wherein said sample application meansis provided with a sample applying nozzle moveable along a straight lineor a circular arc, and the liquid sample take-out positions at whichsaid liquid sample is taken up by said sample application means and thesample applying position at which said liquid sample is applied ontosaid test film are disposed on said straight line or said circular arc.8. An apparatus as defined in claim 4, wherein said sample holding meansholds a plurality of the liquid samples in a ring-shaped area, and saidcentrifugation means the liquid sample prepared thereby on an innerconcentric circle from said ring-shaped area.
 9. A biochemical analysisapparatus comprising:i) a sample holding means for holding a liquidsample and integrally provided with a centrifuging means for receipt ofbody fluid and preparing a liquid sample by centrifugation of the bodyfluid, ii) a test film holding means for holding a plurality of rolls oftest film capable of reacting with said liquid sample to result in achange, iii) a test film conveyance means for each of said rolls of testfilm for sequentially conveying the test film held in said test filmholding means to a predetermined position outside of said test filmholding means, iv) a sample application means for taking up said liquidsample out of said sample holding means and applying a predeterminedamount of said liquid sample onto said test film conveyed to saidpredetermined position, v) an incubator for maintaining thesample-applied portion of said test film at said predetermined positionat a predetermined temperature for a predetermined time, said incubatorincluding an opening through which said sample application means appliessaid liquid sample to said test film, and means for preventing air flowbetween a position inside of said incubator and a position outside ofsaid incubator, said air flow preventing means being reciprocallymovable to cover said opening, and vi) a detection means for measuring achange in optical density of said sample-applied portion of said testfilm situated at said predetermined position based on a reaction productbetween said sample and said test film during or after the passage ofsaid predetermined time, wherein said predetermined position in insidesaid incubator.
 10. An apparatus as defined in claim 9, wherein saidtest film has a comprises an elongated tape.
 11. An apparatus as definedin claim 10, wherein said test film holding means is constituted to holda plurality of elongated tapes, said test film conveyance means, saidincubator and said detection means are provided to correspond to each ofa plurality of said elongated tapes, and a movement means is providedfor moving said sample application means to carry out the sampleapplication to the predetermined position on each of a plurality of saidelongated tapes.
 12. An apparatus as defined in claim 12 wherein saidsample application means is provided with a sample applying nozzlemoveable along a straight line or a circular arc, and the liquid sampletake-out position at which said liquid sample is taken up by said sampleapplication mans and the sample applying position at which said liquidsample is applied onto said test film are disposed on said straight lineor said circular arc.